tbuckley/cabot-search huggingface dataset:
Tislelizumab (Tisle) combined with/without gemcitabine and cisplatin (GC) as adjuvant therapy in patients at high risk after upper urothelial carcinoma (UTUC) surgery: A real-world study.
Authors: Xiaojian Yang, Penghe Quan, Changjiang Yu
Journal: Journal of Clinical Oncology (2023)

e16592 Background: In China, UTUC affects 9.3% - 19.9% of urothelial carcinoma(UC) patients(Pts), comparing to 5%-10% in western countries. Radical nephroureterectomy (RNU) is the standard of care for locally advanced UTUC; however, patient prognosis remains suboptimal, and previous studies have shown a controversial survival benefit of postoperative adjuvant chemotherapy in pts with UTUC. Immune checkpoint inhibitors(ICI) have been demonstrated to improve disease-free survival (DFS) in pts after adjuvant therapy for UC, but the data from UTUC studies is limited. This study is intended to evaluate real-world study data on whether Tisle with/without GC is able to achieve better survival benefit in pts with UTUC. Methods: UTUC pts with clinical diagnosis of T1N1 or T2-T4aN0-1M0, ECOG ps of 0-1, could tolerate surgery and had adequate renal functional reserve after surgery. Enrolled pts underwent RNU surgery and adjuvant therapy was started within 90 days after surgery. ICI: 200 mg in day1(D1), Q3w regimen, when to discontinue the drug was assessed by clinicians, and the reasons for disease progression and intolerable toxicity; GC chemotherapy: gemcitabine 1000 mg/m 2 D1, D8, cisplatin 70 mg/m 2 D2, up to 6 (0-6) cycles. Primary endpoint: 3-year Overall survival (OS) rate; secondary endpoints included 5-year OS rate, tumor-related survival (CSS) and safety. Results: A total of 60 pts received the above treatment from Jan 2020 to Dec 2022, of whom 5 pts were considered to have metastases at initial diagnosis at further evaluation and were finally evaluated for safety only. Fifty-five pts were evaluable for response, with a median follow-up time of 21.5 (3-33) months, and 70.91% (39/55) of pts were followed up for more than 12 months. The OS rate was 93.14% at 1 year and 76.21% at 2 years. Tisle was administered for a median of 6 (1-14) cycles, with a 7.19% and 24.79% lower risk of death at 1 and 2 years in pts with Tisle ≥ 3 cycles compared with pts with Tisle &lt; 3 cycles (HR: 0.368, 95% CI (0.076-1.781); p = 0.162). GC was administered for a median of 3 (0-6) cycles, with a 3.7% and 24.8% lower risk of death at 1 and 2 years in pts with GC＞2 cycles compared with pts with GC≤2 cycles (HR: 0.218, 95% CI (0.045-0.970); p = 0.110). The incidence of treatment-related adverse reactions (trAEs) of any grade was 91.64%; the incidence of trAEs of grade 3-4 was 18.33%, mainly manifested as leukopenic, gastrointestinal reaction and thrombocytopenia. The incidence of immune-related adverse reactions (irAEs) was 25%, and no irAEs of grade 3 or higher were found. The enrollment and follow-up of the present study are currently ongoing. Conclusions: Encouraging efficacy data and safety have been preliminarily observed with adjuvant Tisle with/without GC chemotherapy in high-risk pts after UTUC surgery. Final results also need to be observed in further studies.
Molecular characteristics of <i>KRAS</i> mutations in Chinese patients with cancer.
Authors: Hui Yan, Mengmeng Li, Ningning Luo, Yingxue Qi, Tingting Sun, Chuang Qi
Journal: Journal of Clinical Oncology (2023)

e15070 Background: Sotorasib, the first KRAS G12C inhibitor, has been approved for the treatment of non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation-positive. Understanding the molecular characteristics of KRAS in Chinese patients with cancer is imperative, which is conducive to screening the beneficiary groups. Here, we focus on the molecular characterization of KRAS in NSCLC, colorectal cancer (CRC), pancreatic cancer (PC), and gastric cancer (GC). Methods: This study enrolled 17,775 pan-cancer patients detected by next-generation sequencing (NGS) from June 2021 to February 2022, in which NSCLC, CRC, PC and GC were 48.67% (8651/17775), 10.87% (1933/17775), 1.92% (342/17775) and 5.37% (955/17775), respectively. Results: The KRAS mutation rate in pan-cancer is 16.28% (2893/17775). In NSCLC, CRC, PC and GC cohorts, the mutation rates of KRAS were 13.28% (1149/8651), 50.34% (973/1933), 66.67% (228/342) and 7.64% (73/955), respectively. In NSCLC cohort, 1274 KRAS mutations were detected, and the subtypes were concentrated in G12C (346;27.16%), G12D (205;16.10%), G12V (194;15.23%), G12A (86;6.75) and Q61H (57;4.47%). In CRC cohort, 1094 KRAS mutations were detected. The subtypes were mainly distributed in G12D (350;31.40%), G13D (184;16.82%), G12V (180;16.45%), A146P (66;6.03%) and G12C (49;4.48%). In PC cohort, 251 KRAS mutations were detected, and the subtypes were concentrated in G12D (109;43.43%), G12V (70;27.89%), G12R (32;12.75%), G12C (9;3.59%) and Q61H (9;3.59%). In GC cohort, 82 KRAS mutations were detected. The subtypes of these mutations were concentrated in G12D (23;28.05%), G13D (12;14.63%), Q61H (7;8.54%), G12V (5;6.10%) and Q61R (5;6.10%). Conclusions: In NSCLC, CRC, PC and GC cohorts, K RAS mutations were concentrated in exon 2, accounting for 78.41% (999/1274), 81.63% (893/1094), 91.63% (230/251) and 64.63% (53/82), respectively. In NSCLC cohort, KRAS G12C was the molecular subtype with the highest mutation rate. However, in other cohorts, KRAS G12D was the predominant molecular subtype. G12D mutation will become the next research hotspot, and the breakthrough will help to further expand the beneficiary population of KRAS mutations.
Evaluating clinical trial inclusion/exclusion criteria from claims using generative artificial intelligence.
Authors: Judith Mueller, Ravi Bharat Parikh, Andrew Noble
Journal: Journal of Clinical Oncology (2023)

e13566 Background: Increasing enrollment in oncology clinical trials (CTs) requires identification of trial-eligible patients from routine health data. However, identification of CT-eligible patients is limited by inadequate access to EHR and its relevant clinical features to evaluate inclusion/exclusion (I/E) criteria in large populations. Artificial Intelligence (AI) applied to large-scale administrative claims may accelerate pre-screening of large patient cohorts against common I/E criteria related to stage and performance status (PS). Methods: This retrospective cohort study included 92,895 adult patients from ConcertAI’s real-world data: linked claims and deeply curated de-identified EHRs sourced from data-sharing agreements with 900+ community oncology clinics in the US. Patients had solid malignancies and an oncology encounter between January 6, 2014, and August 12, 2022. Patients with ≥1 claim record within one week of a PS entry and ≥25 claims within three years of a clinical encounter were included. We trained a Generative AI Transformer Model to predict good PS (ECOG 0-1 or Karnofsky 70-100) and stage IV disease at baseline, both of which are common inclusion criteria for therapeutic CTs in advanced malignancies. Model features included 7,745 timestamped claim codes and 8 time-independent demographic and socioeconomic variables. A state-of-the-art Generative AI Pre-trained Transformer Model was fine-tuned via compute-efficient transfer-learning to obtain predictive models for both PS and stage at baseline. The train/validation/test patient split was 95%/2%/3% with 3,039 patients in the PS test set and 2,718 in the stage IV test set. A comparator model was built to predict stage IV at baseline if a C77-9 ICD-100CM secondary malignancy code or cross-walked ICD-9-CM was in the claim record. Results: Among 92,895 patients, 48,331 (52%) were women, 63,620 (68%) were ≥65 years old, 54,495 (59%) were White, and 6,603 (7%) were Black. 38,229 (41%) were confirmed stage IV at baseline and 64,177 (69%) had good PS. In the test set predicting good PS, area under the receiver operating characteristic curve (AUROC) was 0.8 and under the precision-recall curve (AUPRC) was 0.89 for the Generative AI model. This corresponded to an Equal Error Rate (EER) operating point with good precision and recall (both 0.82). Performance metrics for the stage IV endpoint were also acceptable (AUROC 0.84, AUPRC 0.87, EER operating point 0.77). Comparator stage IV precision was 0.73 and recall was 0.47. Conclusions: Generative AI can leverage claims-only data to evaluate common pre-screening I/E criteria in large cohorts and outperforms models based on limited diagnosis codes. Rather than building one model per criterion per indication, Generative AI enables a systematic and reliable solution that can be readily scaled in future large-scale CT screening.
Genetic testing in patients with pancreatic cancer to reveal pathogenic variants in cancer susceptibility genes.
Authors: Nikolaos Tsoulos, Kevisa Potska, Konstantinos Agiannitopoulos, Georgios Tsaousis, Mustafa Ozdogan, Bulent Karabulut, Adina-Emilia Croitoru, Dimitrios C. Ziogas, Maria Theochari, Christos Christodoulou, Epaminondas Samantas, Dimitrios Janinis, Ilias Athanasiadis, Angelos Koutras, Eirini Papadopoulou, George Nasioulas
Journal: Journal of Clinical Oncology (2023)

e16276 Background: Pancreatic cancer is one of the most fatal malignancies. It accounts for 2% of all cancers and 5% of cancer-related deaths. Hence, it is essential to identify pancreatic cancer at an earlier stage to improve outcomes. A variety of hereditary cancer syndromes have been associated with an increased risk of developing pancreatic cancer, and these individuals may benefit from surveillance plans. PARP inhibitor therapy is currently being applied as precision medicine to pancreatic cancer patients harboring germline variant in the Homologous recombination repair (HRR) genes. Our aim was to determine the prevalence of germline pathogenic/likely pathogenic variants in cancer predisposing genes in patients with pancreatic cancer. Methods: In total, 113 patients diagnosed with pancreatic cancer were referred to our laboratory for genetic testing. The analysis of 52 genes involved in hereditary cancer predisposition was performed using a NGS approach. Results: A germline pathogenic/likely pathogenic variant was identified in 20% of patients analyzed. Among individuals with germline pathogenic/likely pathogenic variants, 60% had a positive finding in a pancreatic cancer susceptibility gene; ATM (20%), BRCA1 (20%), BRCA2 (12%), CDKN2A (4%), PALB2 (4%) while 40% carried positive findings in other cancer susceptibility genes. More specifically, in CHEK2 (16%), MRE11 (4%), RAD50 (4%), RAD51C (4%), MUTYH (8%) and NTLH1 (4%). Notably, 84% of pathogenic variants were identified in genes associated with the HRR pathway ( ATM, BRCA1, BRCA2, CHEK2, MRE11, PALB2, RAD50 and RAD51C). Conclusions: Our results indicate that multigene genetic testing is meaningful for pancreatic cancer patients as in 20% of tested individuals we identified findings associated with pancreatic or other cancer predisposition. Moreover, pathogenic/likely pathogenic variants in HRR genes, were identified in 16.6% patients and these patients might benefit from targeted treatments, such as PARP inhibitors or platinum-based treatment.
Effects of ruxolitinib and magrolimab on calreticulin in myelofibrosis CD34+ cells in vitro: Proof of concept for combination therapy.
Authors: Ciro Roberto Rinaldi, Kristian Boasman, Matthew Simmonds
Journal: Journal of Clinical Oncology (2023)

7064 Background: In solid tumours, calreticulin (CALR) overexpression produces a pro-phagocytic signal and is counteracted by concomitant expression of anti- phagocytic CD47, reflecting an apoptosis vs survival mechanism. We have previously found that CD47, not CALR, is overexpressed on the membrane of patients with MPN. Anti-CD47 Magrolimab, is currently being evaluated in clinical trials in AML, MDS but have yet to be tested, either in monotherapy or in combination in MF. Methods: Mononuclear cells were collected by Ficoll separation from bone marrow of 6 MF patients and from 2 controls. CD34+ cells and monocytes were purified using Dynabeads kits from Thermofisher. Cells expression of CALR and CD47 was measured by flow cytometry, before and after incubation with ruxolitinib (Jak inhibitor) alone and in combination with magrolimab. Cells survival was calculated after combining CD34 with monocytes. Informed Consent was obtained for all samples collected. Results: CD47 membrane expression was 57% in untreated MF cells compared to 12% in the control samples and CALR membrane expression was 51.8% in untreated MF cell compared to 12.5% in the control samples. After incubation with ruxolitinib, MF CD34+ cell survival decreased to 98.2%. Following Incubation with magrolimab alone, MF CD34+ cells show no changes in survival (100% alive). The combination of ruxolitinib and magrolimab reduced slightly the MF CD34+ cell survival to 92%. A substantial membrane overexpression of CALR was observed in MF CD34+ cells when incubated with Ruxo and Magrolimab, 74.1%, vs Ruxo alone 52.6%, Magrolimab alone 53.4% and in untreated (51.8%). Interestingly, in the healthy controls, the exposure to combination therapy did not cause the same degree of CALR overexpression (20.7% vs 12.5%), indicating a much stronger pro-phagocytic effect following magrolimab/ruxolitinib combo in MF cancer cells. Conclusions: In vitro, treatment with ruxolitinib or ruxolitinib plus magrolimab, slightly reduce the overall cell survival rate in CD34+ MF samples, comparing with no significant changes in single agent magrolimab. However, the combination of Ruxolitinib and Magrolimab significantly increases CALR membrane expression comparing with Ruxo or Magrolimab alone, signalling a much stronger pro-phagocytic message in MF cells comparing with controls. The induced CALR over-expression, could stimulate a stronger immune response in vivo, where the presence of macrophages would allow removal of CALR rich cells and potentiate the cytoreductive activity towards MF clone. These data support the rational of combining Ruxolitinib with Magrolimab in the next clinical trial stage in myelofibrosis.
The efficacy and safety of donafenib-containing regimens as postoperative adjuvant therapy for hepatocellular carcinoma (HCC): A multicenter retrospective study.
Authors: Jianhua Rao, Xinhua Zhu, Hongwei Zhang, Xin Wei, Yonghua Xu, Long Zhang, Feng Zhang, Xiangcheng Li, Feng Cheng
Journal: Journal of Clinical Oncology (2023)

e16213 Background: Hepatectomy is a key treatment for long-term survival in patients (pts) with HCC, but a high recurrence rate seriously affects the prognosis. Currently, there is no standard treatment for adjuvant therapy, transarterial chemoembolization (TACE), anti-angiogenic therapy, immune checkpoint inhibitor (ICI) therapy, or combination strategies being evaluated. Donafenib as first-line systemic therapy is recommended in advanced HCC, but this as adjuvant therapy is still explored. This study evaluated the efficacy and safety of donafenib-containing regimens as postoperative adjuvant therapies in HCC. Methods: We retrospectively reviewed the data of pts who had received donafenib monotherapy (D) or a combined regimen (D+TACE, D+ICI, or D+TACE+ICI) as adjuvant therapy in 5 Chinese centers from June 2021 to December 2022. Recurrence was assessed using imaging. A high-risk (HR) subpopulation was defined as pts with any of the following conditions: [i] single lesion &gt;5 cm or multiple lesions of any size; [ii] lesion(s) complicated by tumor thrombus (TT); and [iii] microvascular invasion (MVI) grade ≥1. We analyzed the median relapse-free survival (mRFS) and one-year cumulative recurrence-free survival rate (1y-RFS) of the overall population and HR subpopulation, and safety (CTCAE5.0) of the overall population. Results: This study included 102 pts. At the data cut-off, mRFS had not yet been achieved, with a 1y-RFS rate of 78.2%; 12 pts (11.8%) experienced recurrence. In the HR subpopulation (N=80), the 1y-RFS rate was 79.4%, based on different treatment regimens, the 1y-RFS rates of the D (n=20), D+TACE (n=26), D+ICI (n=23), and D+TACE+ICI (n=11) groups were 87.5%, 87.7%, 72.4%, and 74.1%, respectively, and mRFS had not yet been reached; based on different clinical stages, the 1y-RFS rates of pts with China liver cancer staging stage Ib (n=35) and IIa (n=15) were 93.3% and 71.6%, respectively, with stage Ⅰa (n=12) and Ⅱb (n=7) were not reached, mRFS with IIIa (n=11) was 8.9 months (95% CI: 2.9–15.0 months). Among the overall population, 68 pts (66.7%) had treatment-related adverse events (TRAE) of any grade, and the incidence of grade 3 TRAE was 8.8% (9/102). None of the pts experienced grade 4 or 5 TRAE. Conclusions: These results preliminarily showed that donafenib-containing regimens as postoperative adjuvant therapies were safe and effective for HCC. [Table: see text]
Acute lymphocytic leukemia incidence and survivability trends in the United States over the last two decades: SEER data set from 2000-2019.
Authors: Ishan Ghosh, Sudipto Mukherjee
Journal: Journal of Clinical Oncology (2023)

e19050 Background: The primary objective of this study is to evaluate how race, age at which patients were diagnosed, sex, and phenotype affect incidence and survivability for acute lymphocytic leukemia (ALL) patients in the United States. Keeping these factors in consideration this study was developed to see how existing cancer registry data can assist us in early detection of ALL in patients. Our hypothesis was that statistically significant correlations exist between race, age at which patients were diagnosed, sex, and phenotype of the ALL patients. Methods: The rate of incidence and survivability data were evaluated using SEER*Stat statistical software from National Cancer Institute. For incidence calculation we used the SEER 22 registry that covered approximately 47.99% of the U.S. population, while survival statistics were calculated using the SEER 17 registry that covered 26.5% of the U.S. population, both containing records from 2000 through 2019. In calculating the incidence statistics only the first primary tumor and reported diagnosis of the disease was accounted for. Results: There were statistically significant correlations between sex, race/ethnicity, age at which patients were diagnosed, phenotype of the ALL patient, and their rate of incidence. Analysis of All incidence data showed that the disease was more prevalent among Caucasian population. Among ALL patients, 59% patients were between 0 to 19 years of age when diagnosed, and 56% were male. ALL are mostly associated in patients with B-cell phenotype (73%). Evaluation of survivability data showed a slightly higher 5-year survival rate than 10-year survival rate. Conclusions: Survivability rates of African Americans patients were the lowest compared to Caucasian, Asian, Pacific Islanders, Alaskan Native, Native Americans and others. Survivability rates progressively decreased for older patients. Additionally, this study looked into the common treatment approaches that were administered in ALL patients which primarily included chemotherapy supplemented with some form of radiation therapy, as and when needed. The study showed chemotherapy was quite effective in improving patients’ survival probabilities, while the prognosis from the disease was not quite good for those who did not receive any treatment. This updated study on ALL incidence, survival rate, and common treatment options will further assist the health care professionals in effectively screening potential patients, their early detection, and in implementing a successful treatment regimen. This could potentially improve survival rates among those diagnosed at an older age who have a far greater mortality rate from ALL compared to younger patients.
Erdafitinib (ERDA) vs ERDA plus cetrelimab (ERDA+CET) for patients (pts) with metastatic urothelial carcinoma (mUC) and fibroblast growth factor receptor alterations (FGFRa): Final results from the phase 2 Norse study.
Authors: Arlene O. Siefker-Radtke, Thomas Powles, Victor Moreno, Taek Won Kang, Irfan Cicin, Angela Girvin, Sydney Akapame, Spyros Triantos, Anne O'Hagan, Wei Zhu, Meggan Tammaro, Yohann Loriot
Journal: Journal of Clinical Oncology (2023)

4504 Background: First-line (1L) therapy for cisplatin (cis)-ineligible pts with mUC remains an unmet need and includes alternative chemotherapy or anti-PD-(L)1 monotherapy for PD-L1 positive tumors. FGFRa tumors are enriched for the luminal 1 subtype with lower immune cell infiltrate and potential lower benefit from anti-PD-(L)1 monotherapy. We studied ERDA+CET in 1L, FGFRa, mUC to determine the potential impact in this setting (NCT03473743). Methods: Pts aged ≥ 18 y with mUC, susceptible FGFRa and measurable disease (no prior systemic therapy for mUC, cis-ineligible) were randomized 1:1 to once-daily ERDA 8 mg (with pharmacodynamically guided uptitration (UpT) to 9 mg) or ERDA 8 mg (no UpT) + IV CET 240 mg every 2 weeks (wks) at cycles 1-4 and 480 mg every 4 wks thereafter. Primary endpoints were investigator-assessed overall response rate (ORR) per RECIST 1.1 and safety; secondary included duration of response (DOR), time to response (TTR), progression free survival (PFS) and overall survival (OS). There were no pre-planned statistical comparisons between treatment arms. Results: As of the data cutoff, 87 pts were randomized and treated; 44 to ERDA+CET and 43 to ERDA: median age was 69 vs 72 y; visceral metastases were present in 60.0 vs 63.6%. Median follow-up time was 14.2 months (mo). ORR for ERDA+CET was 54.5% with 6 (13.6%) CRs and 12 mo OS 68%. 11/24 responders were ongoing. ORR for ERDA was 44.2% with 1 CR and 12 mo OS 56%. 9/19 responders were ongoing. 4 pts in each arm were PD-L1 positive. 3/4 (75%) PD-L1 positive pts responded to ERDA+CET vs 0 for ERDA. The most frequent treatment-emergent AEs (any grade) were hyperphosphatemia (68.9 vs 83.7%), stomatitis (59.1 vs 72.1%) and diarrhea (45.5 vs 48.8%) for ERDA+CET and ERDA respectively. Grade ≥3 treatment-related AEs occurred in 45.5 (ERDA+CET) and 46.5% (ERDA) of pts. There was one CET-related death in ERDA+CET secondary to pulmonary failure. Conclusions: Combination ERDA+CET demonstrated clinically meaningful activity and was well tolerated. These results, in 1L cis-ineligible pts, support previously described activity of ERDA monotherapy in FGFRa mUC. The safety profile was consistent with the known profile for ERDA and CET with no additive toxicity for the combination. Clinical trial information: NCT03473743 . [Table: see text]